Phosphatidylinositol 3-kinase-related kinase

Phosphatidylinositol 3-kinase-related kinases (PIKKs) are a family of Ser/Thr-protein kinases with sequence similarity to phosphatidylinositol-3 kinases (PI3Ks).[1]

Members

The human PIKK family includes six members:

Gene Protein Function
ATM ataxia-telangiectasia mutated response to DNA damage
ATR ataxia- and Rad3-related "
PRKDC DNA-dependent protein kinase catalytic subunit (DNA-PKcs) "
FRAP1 mammalian target of rapamycin (mTOR) nutrient-regulated kinase that controls metabolism and cell growth
SMG1 suppressor of morphogenesis in genitalia regulates nonsense-mediated mRNA decay
TRRAP transformation/transcription domain-associated protein transcription factor co-activator

Structure

PIKKs proteins contain the following four domains:

  1. N-terminus FRAP-ATM- TRRAP (FAT) domain, Pfam PF02259
  2. kinase domain (KD; PI3_PI4_kinase),
  3. PIKK- regulatory domain (PRD), and
  4. C-terminus FAT-C-terminal (FATC) domain Pfam PF02260

References

  1. Lempiäinen H, Halazonetis TD (October 2009). "Emerging common themes in regulation of PIKKs and PI3Ks". EMBO J. 28 (20): 3067–73. doi:10.1038/emboj.2009.281. PMC 2752028. PMID 19779456.